Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

Differentiation of Crohn’s disease from intestinal tuberculosis in India in 2010

Differentiating intestinal tuberculosis from Crohn’s disease (CD) is an important clinical challenge of considerable therapeutic significance. The problem is of greatest magnitude in countries where tuberculosis continues to be highly prevalent, and where the incidence of CD is increasing. The final clinical diagnosis is based on a combination of the clinical history with endoscopic studies, culture and polymerase chain reaction for Mycobacterium tuberculosis, biopsy pathology, radiological investigations and response to therapy. In a subset of patients, surgery is required and intraoperative findings with pathological study of the resected bowel provide a definitive diagnosis. Awareness of the parameters useful in distinguishing these two disorders in each of the different diagnostic modalities is crucial to accurate decision making. Newer techniques, such as capsule endoscopy, small bowel enteroscopy and immunological assays for Mycobacterium tuberculosis, have a role to play in the differentiation of intestinal tuberculosis and CD. This review presents currently available evidence regarding the usefulness and limitations of all these different modalities available for the evaluation of these two disorders.

Per oral cholangiopancreatoscopy in pancreatico biliary diseases- Expert consensus statements

AIM: To provide consensus statements on the use of per-oral cholangiopancreatoscopy(POCPS).METHODS: A workgroup of experts in endoscopic retrograde cholangiopancreatography(ERCP), endosonography, and POCPS generated consensus statements summarizing the utility of POCPS in pancreaticobiliary disease. Recommendation grades used validated evidence ratings of publications from an extensive literature review.RESULTS: Six consensus statements were generated:(1) POCPS is now an important additional tool during ERCP;(2) in patients with indeterminate biliary strictures, POCS and POCS-guided targeted biopsy are useful for establishing a definitive diagnosis;(3) POCS and POCS-guided lithotripsy are recommended for treatment of difficult common bile duct stones when standard techniques fail;(4) in patients with main duct intraductal papillary mucinous neoplasms(IPMN) POPS may be used to assess extent of tumor to assist surgicalresection;(5) in difficult pancreatic ductal stones,POPS-guided lithotripsy may be useful in fragmentation and extraction of stones; and(6) additional indications for POCPS include selective guidewire placement,unexplained hemobilia, assessing intraductal biliary ablation therapy, and extracting migrated stents. CONCLUSION: POCPS is important in association with ERCP, particularly for diagnosis of indeterminate biliary strictures and for intra-ductal lithotripsy when other techniques failed, and may be useful for preoperative assessment of extent of main duct IPMN, for extraction of difficult pancreatic stones, and for unusua indications involving selective guidewire placement,assessing unexplained hemobilia or intraductal biliary ablation therapy, and extracting migrated stents.

Gastroenterology training in private hospitals:India vs South Africa

In South Africa,nurses and doctors are emigrating in significant numbers. Job satisfaction,safety and ensuring career progression are important in retaining doctors to make a career in Republic of South Africa (RSA). Due to budgetary constraints many hospitals have not been upgraded. Coming home after overseas training seems difficult. In RSA it takes a minimum of 13 years for a young specialist to become registered and 15 years for subspecialists. Career progression,creating more specialist trainees in public and private hospitals and shortening the period of professional training are potential solutions to the problem. India,which has a population of more than 1 billion people,is struggling with similar problems. For the past 10-15 years,private hospitals have assisted in manpower development for medical specialist and subspecialist careers. Currently their private sector trains 60% of their recognised (sub)specialities fellows. A national task force for specialist training in RSA should be instituted. It should discuss,based on the current status and projected specialist and subspecialist personnel requirements,thefuture structure and logistics of training needs. This is required in all subspecialities including gastroenterology,as has been done in India. It is hoped that as a consequence well-trained doctors,similar to those in India,might move to provincial hospitals in rural areas,upgrading the medical services and keeping medical power in South Africa. South Africa should become a model for Sub-Saharan Africa,as India already is for South-East Asia.

Regional differences in genetic susceptibility to nonalcoholic liver disease in two distinct Indian ethnicities

AIM To validate the association of variants in PNPLA3(rs2281135) and TM6SF2(rs58542926) genes with ultrasound detected non-alcoholic fatty liver disease(NAFLD).METHODS A total of 503 individuals with and without fatty infiltration were recruited. Fatty infiltration was confirmed based on ultrasound findings. Anthropometric data and blood samples were collected from the study group. DNA was isolated from peripheral blood, quality and quantity was assessed by gel electrophoresis and spectrophotometer respectively. Genotyping of the variants in PNPLA3 and TM6SF2 genes was carried out by employing taqman probes(C_15875080_10 for PNPLA3 and C_8946351_10 for TM6SF2 SNP) on real time PCR(Stepone-Lifetechnologies). Genotype data was tested for deviations from Hardy-Weinbergequilibrium. χ~2 test was used to analyze the statistical significance of the difference in genotype distribution of the studied variants in patients and controls and the strength of association was expressed as odds ratio(95%CI). A two-tailed P value of ≤ 0.05 was considered statistically significant. RESULTS The study group comprised of 503 individuals of which 256 had fatty infiltration and 247 without fatty infiltration and thus formed the patient and control groups respectively. As the patient group could be divided in to two distinct ethnicities(ancestral South Indians-ASI and North-East Indians-NEI), further recruitment of control cohort and association analyses was carried out based on ethnicities. Of the 256 with fatty infiltration 93 were ASI and 163 were NEI and of the 247 controls 138 were ASI and 109 were NEI. As expected, there were significant differences in the anthropometric and other clinical data between the control and the patient groups. However significant differences within the ethnicities were also noted. While rs2281135 in PNPLA3 gene was significantly associated(P = 0.03) with higher risk(odds 1.9, 95%CI: 1.5-3.14, P = 0.03) of NAFLD in NEI ethnicity, rs58542926 in TM6SF2 gene was significantly associated with NAFLD with a 2.7 fold higher risk(odds 2.7, 95%CI: 1.37-5.3, P = 0.0004) of the disease. There were significantly higher proportions of individuals with variants in both the genes in the patient group in both ASI(patients-14/93 and controls-7/138; P = 0.009) and NEI ethnicities(patients-17/163 and controls-7/109; P = 0.01). CONCLUSION Although the study identified distinct genetic susceptibility in the two ethnicities, transheterozygosity of the variants suggests higher risk of NAFLD in individuals with both the variants.